Ultrastructural Features of Apoptosis

Apoptosis is a gene-directed physiological and programmed process of cell deletion aimed at the regulation of tissue and organ development. It affects different cell types and is triggered by a variety of stimuli all inducing closely comparable structural changes. Despite the deeply different morphology and metabolism of the cell models and the various inducers and their initial effects, a convergence seems to take place in a common metabolic pathway that, in most cases, involves the activation of a Ca2+ dependent endonuclease. A growing body of data is now available on the molecular events that lead to DNA damage. DNA cleavage in nucleosomic or oligonucleosomic fragments is related to the appearance of unusual and very characteristic ultrastructural changes. The nucleus is especially affected, and shows chromatin rearrangements consisting of cup-shaped marginations, sharply separated from diffuse chromatin areas. Nuclear fragmentation subsequently appears, finally followed by the formation of numerous micronuclei. Cytoplasmic damage appears at a very late stage and the process takes place despite good preservation of plasma membrane and cytoplasm

hypophosphatemia in patients with chronic hbv

Phosphorus is an essential element for correct functioning of the organism. Alteration of serum phosphorus may be due to reduced dietary intake, altered by intra-extracellular, by excretion or reabsorption from the intestine, bone and kidney. In patients with chronic hepatitis B, hypophosphatemia may be secondary to several causes among which the most frequent are related to the use of drugs and the deficiency of vitamin D. Tenofovir is a first choice drug for the treatment of chronic hepatitis B and it can be used in patients with mild renal impairment. In fact renal failure induced by TDF is not frequent, dose-dependent and usually reversible. However, it's recommended to avoid use other nephrotoxic drugs during treatment with TDF; monitor kidney function and phosphorus metabolism before and during therapy; adjust the doses of the drugs to the degree of renal failure; verify the presence of proximal tubulopathy through the calculation of the EFPi and the TMPi/GFR and consider the suspension of the TDF in the case of severe hypophosphoremia (< 1 mg / dl) or creatinine clearance < 50 ml/min). The aim of this review is to facilitate the recognition of druginduced hypophosphatemia and differentiate it from that due to other causes, in order to avoid unnecessary discontinuation of antiviral therapy

Nuclear pores in the apoptotic cell.

During apoptosis, nuclear pores undergo strong modifications, which are described here in five different apoptotic models, Conventional electron microscopy, supported by freeze-fracture analysis, showed a constant migration of nuclear pores towards the diffuse chromatin areas, In contrast, dense chromatin areas appear pore-free and are frequently surrounded by strongly dilated cistemae, A possible functional significance of this pore behaviour during apoptosis is discussed

Management of Painful Shoulder Arthroplasty: A Narrative Review

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Interactions of GFAP with ceftriaxone and phenytoin: SRCD and molecular docking and dynamic simulation

Abstract Background GFAP is the major intermediate filament protein in mature astrocytes. Its increased expression and aggregation was firstly associated to Alexander's disease, and successively in different neurological diseases including scrapie, Alzheimer's and Creutzfeld–Jacob diseases. Recently, ceftriaxone a multi-potent β-lactam antibiotic able to overcome the blood–brain barrier, successfully eliminated the cellular toxic effects of misfolded mutated GFAP, similarly to phenytoin sodium, in a cellular model of Alexander's disease and inhibited α-synuclein aggregation protecting PC12 cells from the exposure to 6-hydroxydopamine. Methods In this study, synchrotron radiation circular dichroism spectroscopy has been used to obtain structural information about the GFAP-ceftriaxone (phenytoin) interactions, while computational methods allowed the identification of the relevant putative binding site of either ceftriaxone or phenytoin on the dimer structure of GFAP, permitting to rationalize the spectroscopic experimental results. Results We found that GFAP exhibited enhanced stability upon the addition of two equivalents of each ligands with ceftriaxone imparting a more spontaneous interactions and a more ordered complex system than phenytoin. Conclusions SRCD data and MD models indicate a stronger protective effect of ceftriaxone in neurological disorders characterized by an increased production and polymerization of GFAP. General significance This result, in addition to our previous works in which we documented that ceftriaxone interacts with α-synuclein inhibiting its pathological aggregation and that a cyclical treatment with this molecule in a patient with adult-onset Alexander's disease halted, and partly reversed, the progression of neurodegeneration, suggests the possibility of a chaperone-like effect of ceftriaxone on protein involved in specific neurodegenerative diseases

A Stage-Based Approach to Therapy in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder that features progressive, disabling motor symptoms, such as bradykinesia, rigidity, and resting tremor. Nevertheless, some non-motor symptoms, including depression, REM sleep behavior disorder, and olfactive impairment, are even earlier features of PD. At later stages, apathy, impulse control disorder, neuropsychiatric disturbances, and cognitive impairment can present, and they often become a heavy burden for both patients and caregivers. Indeed, PD increasingly compromises activities of daily life, even though a high variability in clinical presentation can be observed among people affected. Nowadays, symptomatic drugs and non-pharmaceutical treatments represent the best therapeutic options to improve quality of life in PD patients. The aim of the present review is to provide a practical, stage-based guide to pharmacological management of both motor and non-motor symptoms of PD. Furthermore, warning about drug side effects, contraindications, as well as dosage and methods of administration, are highlighted here, to help the physician in yielding the best therapeutic strategies for each symptom and condition in patients with PD

The mitogenome of the jumping bristletail Trigoniophthalmus alternatus (Insecta, Microcoryphia) and the phylogeny of insect early-divergent lineages

The complete mitochondrial genome of the machilid Trigoniophthalmus alternatus (Silvestri 1904) is herein described and applied to phylogenetic analyses, inclusive of the most early-divergent lineages of hexapods. Both gene content and order generally conform with the organization of the arthropods’ mitochondrial genome. One gene translocation involving trnA is the autapomorphic character observed in this species. Another peculiar molecular feature is the long size of the A + T-rich region, due to the occurrence of repeat units. The phylogenetic analyses support the typical placement, along the hexapods’ tree, of Ectognatha, Monocondylia and Dicondylia, with Diplura as the adelphotaxon of all true insects

The mitochondrial genome of the springtail Bourletiella arvalis (Symphypleona, Collembola)

The complete mitochondrial genome of the springtail Bourletiella arvalis (Fitch, 1863) is herein described and applied to a Bayesian phylogenetic analysis, inclusive of all the Collembola mitochon- drial DNAs sequenced so far. The gene content and order, as well as the nucleotide composition, con- form with the well-known features of hexapods’ mitochondrial genomes. The phylogenetic analysis supports the monophyly of Collembola, Poduromorpha, Entomobryomorpha and Symphypleona. However, no mtDNA from Neelipleona is available to date, therefore limiting the application of mito- chondrial genomes to further investigate springtail systematics

Adolescent idiopathic scoliosis screening: Could a school-based assessment protocol be useful for an early diagnosis?

BACKGROUND: Adolescent idiopathic scoliosis screening still needs a considerable implementation, particularly throughout a school-based assessment protocol. OBJECTIVE: This study aims to evaluate the effectiveness of clinical examinations currently in use for the diagnosis of adolescent idiopathic scoliosis, through a survey carried out in secondary schools to standardize a screening protocol that could be generalized. METHODS: In their classrooms, the adolescents underwent an idiopathic scoliosis screening through three examinations: Adam’s test, axial trunk rotation (ATR) and plumb line. In case of single positivity to one of the three examinations, a column X-ray examination was recommended. RESULTS: The sensitivity and diagnostic specificity of Adam’s test or ATR were 56.3% and 92.7%, respectively. The positivity to at least one between ATR or plumb line showed that sensitivity was higher than specificity: 91.3% versus 80.8%; the positivity to at least one between Adams’s test or plumb line showed a sensitivity of 95.2% and a specificity of 81.5%. Finally, the positivity to all three examinations showed an increase in specificity (99.7%). CONCLUSIONS: Taken together, our findings show that this school-based screening protocol had a very high specificity in early diagnosis of adolescent idiopathic scoliosis